Serine Protease Inhibitors Modulate Smoke-Induced Chemokine Release from Human Lung Fibroblasts

Hiroki Numanami, Sekiya Koyama, Dan K. Nelson, Jeffrey C. Hoyt, Jon L. Freels, Michael P Habib, Jun Amano, Masayuki Haniuda, Etsuro Sato, Richard A. Robbins

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Smoking is associated with lung inflammation and a protease-antiprotease imbalance. We previously reported that cigarette smoke extract (CSE) stimulates human lung fibroblasts to release chemotactic cytokines. We hypothesized that serine protease inhibitors might modulate lung fibroblast release of chemotactic cytokines in response to CSE. To test this hypothesis, serine protease inhibitors (FK706, α1-antitrypsin, methoxysuccinyl-Ala-Ala-Pro- Val chloromethyl ketone, or Nα-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) and monocyte chemotactic activity (MCA) from human fetal lung fibroblasts by the blind-well chemotactic chamber. Metalloproteinases and cysteine proteinases were not examined in this study. Similarly, the release and gene expression of chemokines and nuclear factor-κB (NF-κB) activation were measured by means of enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Release of NCA, MCA, chemotactic chemokines including interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor, and the expression of interleukin-8 and monocyte chemoattractant protein-1 mRNA were attenuated by FK706. Furthermore, FK706 suppressed NF-κB activation. These data suggest that serine protease inhibitors attenuate the CSE-induced release of NCA and MCA from human fetal lung fibroblasts and that the inhibitory action of antiproteases might depend on NF-κB signaling pathway.

Original languageEnglish (US)
Pages (from-to)613-619
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume29
Issue number5
DOIs
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

Serine Proteinase Inhibitors
Fibroblasts
Chemokines
Smoke
Tobacco Products
Monocytes
Fetal Movement
Lung
Neutrophils
Chemokine CCL2
Protease Inhibitors
Interleukin-8
Human Activities
Chemical activation
Immunosorbents
Cysteine Proteases
Polymerase chain reaction
RNA-Directed DNA Polymerase
Metalloproteases
Granulocyte Colony-Stimulating Factor

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Serine Protease Inhibitors Modulate Smoke-Induced Chemokine Release from Human Lung Fibroblasts. / Numanami, Hiroki; Koyama, Sekiya; Nelson, Dan K.; Hoyt, Jeffrey C.; Freels, Jon L.; Habib, Michael P; Amano, Jun; Haniuda, Masayuki; Sato, Etsuro; Robbins, Richard A.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 29, No. 5, 11.2003, p. 613-619.

Research output: Contribution to journalArticle

Numanami, H, Koyama, S, Nelson, DK, Hoyt, JC, Freels, JL, Habib, MP, Amano, J, Haniuda, M, Sato, E & Robbins, RA 2003, 'Serine Protease Inhibitors Modulate Smoke-Induced Chemokine Release from Human Lung Fibroblasts', American Journal of Respiratory Cell and Molecular Biology, vol. 29, no. 5, pp. 613-619. https://doi.org/10.1165/rcmb.2003-0113OC
Numanami, Hiroki ; Koyama, Sekiya ; Nelson, Dan K. ; Hoyt, Jeffrey C. ; Freels, Jon L. ; Habib, Michael P ; Amano, Jun ; Haniuda, Masayuki ; Sato, Etsuro ; Robbins, Richard A. / Serine Protease Inhibitors Modulate Smoke-Induced Chemokine Release from Human Lung Fibroblasts. In: American Journal of Respiratory Cell and Molecular Biology. 2003 ; Vol. 29, No. 5. pp. 613-619.
@article{3b6914e8254448f3ba59c8f9987e39f8,
title = "Serine Protease Inhibitors Modulate Smoke-Induced Chemokine Release from Human Lung Fibroblasts",
abstract = "Smoking is associated with lung inflammation and a protease-antiprotease imbalance. We previously reported that cigarette smoke extract (CSE) stimulates human lung fibroblasts to release chemotactic cytokines. We hypothesized that serine protease inhibitors might modulate lung fibroblast release of chemotactic cytokines in response to CSE. To test this hypothesis, serine protease inhibitors (FK706, α1-antitrypsin, methoxysuccinyl-Ala-Ala-Pro- Val chloromethyl ketone, or Nα-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) and monocyte chemotactic activity (MCA) from human fetal lung fibroblasts by the blind-well chemotactic chamber. Metalloproteinases and cysteine proteinases were not examined in this study. Similarly, the release and gene expression of chemokines and nuclear factor-κB (NF-κB) activation were measured by means of enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Release of NCA, MCA, chemotactic chemokines including interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor, and the expression of interleukin-8 and monocyte chemoattractant protein-1 mRNA were attenuated by FK706. Furthermore, FK706 suppressed NF-κB activation. These data suggest that serine protease inhibitors attenuate the CSE-induced release of NCA and MCA from human fetal lung fibroblasts and that the inhibitory action of antiproteases might depend on NF-κB signaling pathway.",
author = "Hiroki Numanami and Sekiya Koyama and Nelson, {Dan K.} and Hoyt, {Jeffrey C.} and Freels, {Jon L.} and Habib, {Michael P} and Jun Amano and Masayuki Haniuda and Etsuro Sato and Robbins, {Richard A.}",
year = "2003",
month = "11",
doi = "10.1165/rcmb.2003-0113OC",
language = "English (US)",
volume = "29",
pages = "613--619",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "5",

}

TY - JOUR

T1 - Serine Protease Inhibitors Modulate Smoke-Induced Chemokine Release from Human Lung Fibroblasts

AU - Numanami, Hiroki

AU - Koyama, Sekiya

AU - Nelson, Dan K.

AU - Hoyt, Jeffrey C.

AU - Freels, Jon L.

AU - Habib, Michael P

AU - Amano, Jun

AU - Haniuda, Masayuki

AU - Sato, Etsuro

AU - Robbins, Richard A.

PY - 2003/11

Y1 - 2003/11

N2 - Smoking is associated with lung inflammation and a protease-antiprotease imbalance. We previously reported that cigarette smoke extract (CSE) stimulates human lung fibroblasts to release chemotactic cytokines. We hypothesized that serine protease inhibitors might modulate lung fibroblast release of chemotactic cytokines in response to CSE. To test this hypothesis, serine protease inhibitors (FK706, α1-antitrypsin, methoxysuccinyl-Ala-Ala-Pro- Val chloromethyl ketone, or Nα-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) and monocyte chemotactic activity (MCA) from human fetal lung fibroblasts by the blind-well chemotactic chamber. Metalloproteinases and cysteine proteinases were not examined in this study. Similarly, the release and gene expression of chemokines and nuclear factor-κB (NF-κB) activation were measured by means of enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Release of NCA, MCA, chemotactic chemokines including interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor, and the expression of interleukin-8 and monocyte chemoattractant protein-1 mRNA were attenuated by FK706. Furthermore, FK706 suppressed NF-κB activation. These data suggest that serine protease inhibitors attenuate the CSE-induced release of NCA and MCA from human fetal lung fibroblasts and that the inhibitory action of antiproteases might depend on NF-κB signaling pathway.

AB - Smoking is associated with lung inflammation and a protease-antiprotease imbalance. We previously reported that cigarette smoke extract (CSE) stimulates human lung fibroblasts to release chemotactic cytokines. We hypothesized that serine protease inhibitors might modulate lung fibroblast release of chemotactic cytokines in response to CSE. To test this hypothesis, serine protease inhibitors (FK706, α1-antitrypsin, methoxysuccinyl-Ala-Ala-Pro- Val chloromethyl ketone, or Nα-p-tosyl-L-lysine chloromethyl ketone) were evaluated for their capacity to attenuate the release of neutrophil chemotactic activity (NCA) and monocyte chemotactic activity (MCA) from human fetal lung fibroblasts by the blind-well chemotactic chamber. Metalloproteinases and cysteine proteinases were not examined in this study. Similarly, the release and gene expression of chemokines and nuclear factor-κB (NF-κB) activation were measured by means of enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Release of NCA, MCA, chemotactic chemokines including interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor, and the expression of interleukin-8 and monocyte chemoattractant protein-1 mRNA were attenuated by FK706. Furthermore, FK706 suppressed NF-κB activation. These data suggest that serine protease inhibitors attenuate the CSE-induced release of NCA and MCA from human fetal lung fibroblasts and that the inhibitory action of antiproteases might depend on NF-κB signaling pathway.

UR - http://www.scopus.com/inward/record.url?scp=0242351212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0242351212&partnerID=8YFLogxK

U2 - 10.1165/rcmb.2003-0113OC

DO - 10.1165/rcmb.2003-0113OC

M3 - Article

C2 - 12738688

AN - SCOPUS:0242351212

VL - 29

SP - 613

EP - 619

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 5

ER -